Lasting DNA Damage and Aberrant DNA Repair Gene Expression Profile Are Associated with Post-Chronic Cadmium Exposure...

Cadmium (Cd) is a widespread environmental pollutant and carcinogen. Although the exact mechanisms of Cd-induced carcinogenesis remain unclear, previous acute/chronic Cd exposure studies have shown that Cd exerts its cytotoxic and carcinogenic effects through multiple mechanisms, including interference with the DNA repair system. However, the effects of post-chronic Cd exposure remain unknown. Here, we establish a unique post-chronic Cd-exposed human lung cell model (the "CR0" cells) and investigate the effects of post-chronic Cd exposure on the DNA repair system. We found that the CR0 cells retained Cd-resistant property even though it was grown in Cd-free culture medium for over a year. The CR0 cells had lasting DNA damage due to reduced DNA repair capacity and an aberrant DNA repair gene expression profile. A total of 12 DNA repair genes associated with post-chronic Cd exposure were identified, and they could be potential biomarkers for identifying post-chronic Cd exposure. Clinical database analysis suggests that some of the DNA repair genes play a role in lung cancer patients with different smoking histories. Generally, CR0 cells were more sensitive to chemotherapeutic (cisplatin, gemcitabine, and vinorelbine tartrate) and DNA damaging (H₂O₂) agents, which may represent a double-edged sword for cancer prevention and treatment. Overall, we demonstrated for the first time that the effects of post-chronic Cd exposure on human lung cells are long-lasting and different from that of acute and chronic exposures. Findings from our study unveiled a new perspective on Cd-induced carcinogenesis-the post-chronic exposure of Cd. This study encourages the field of post-exposure research which is crucial but has long been ignored.